I intend to study the extent to which the lifespan of a multicellular organism, the small roundworm, Caenorhabditis elegans, is subject to alteration by mutation. Since a wide variety of harmful mutations having nothing to do with the normal processes of aging could shorten the lifespan, my basic method of attack will be to look for mutant organisms that live longer than normal. If such mutants can be isolated, I will investigate: 1) Their genetics: I will ask how many mutant genes there are that can increase lifespan; by how much single mutant genes can increase lifespan; how lifespan mutations interact with one another; and whether mutations to long lifespan are dominant. 2) Their development: I will ask whether lifespan mutants develop at the same rate as the wild type during the various stages of their life cycle. 3) Their biochemistry: I will investigate the metabolic rate, mitochondrial function, rates of protein and DNA turnover and specific activity of enzymes in lifespan mutants. I will look for lifespan mutants as follows: a) I will establish 1000 or more clones derived from independently mutagenized nematodes. (This is easily done because C. elegans is a self-fertilizing hermaphrodite, i.e. each worm normally fertilizes its own eggs.) I will then establish synchronous subpopulations of the clones, let these populations age, and then look for clones whose individuals are alive longer than normal. b) I will look for mutants that are fertile longer than normal by mutagenizing and synchronizing a culture, allowing the culture to reproduce, and retaining the progeny that are produced at very late times. I will then study these longer-fertile mutants to see if they have longer lifespans. c) I will characterize in detail properties of the wild-type organism that change with age such as rate of movement, sensitivities to drugs, and sensitivities to osmotic shock. Using this knowledge, I will try to select mutants in which these age-related properties develop less quickly than in the wild type.